An experimental injection known as CBL-514 has demonstrated the ability to trigger fat cells to self-destruct, leading to significant reductions in dangerous abdominal fat during early human trials. The findings were presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, by researchers from the University of Alabama at Birmingham and Caliway Biopharmaceuticals.
Unlike traditional weight loss medications that primarily reduce the amount of fat stored within existing cells, CBL-514 targets adipocytes directly. The drug induces apoptosis, a natural biological process that causes cells to break down and die. This mechanism allows the treatment to reduce both subcutaneous fat, which sits beneath the skin, and visceral fat, which surrounds internal organs like the liver and intestines.
Clinical Results Show Significant Fat Loss
Researchers analyzed data from two phase 2 clinical trials, designated CBL-0204 and CBL-0205, to measure the drug’s impact on visceral abdominal fat. The studies involved participants with a body mass index (BMI) between 22 and 30 kg/m2. Patients received injections into the lower abdomen every three weeks for up to 12 weeks, with doses reaching up to 600 mg. Treatment continued until the fat layer fell below a specified thickness threshold.
Magnetic resonance imaging (MRI) scans were used to measure changes in fat volume before treatment and at follow-up intervals. At the eight-week follow-up for subcutaneous fat, 69.6% of participants treated with CBL-514 lost at least 150 mL of fat volume. None of the participants in the placebo group reached this threshold.
The effects on visceral fat were similarly pronounced. Four weeks after the final injection, participants in the CBL-514 group experienced an average 12.01% reduction in visceral fat volume compared to their baseline measurements. In contrast, the placebo group showed an average increase of 5.68%. This created a 17.69 percentage point difference between the two groups.
At the later follow-up, conducted eight to 12 weeks after treatment ended, the CBL-514 group maintained an average visceral fat volume 10.45% below baseline. The placebo group had increased by 11.76%, resulting in a 22.21 percentage point difference. These results suggest that the injection’s effects on visceral fat persistence lasted for several weeks after the treatment concluded.
Potential for Weight Maintenance After Drug Cessation
Dr. W. Timothy Garvey of the University of Alabama at Birmingham highlighted that these findings raise the possibility that CBL-514 could help patients maintain weight loss after discontinuing popular GLP-1 receptor agonist medications. Drugs such as Ozempic, Wegovy, Mounjaro, and Zepbound have transformed obesity treatment but often lead to weight regain once patients stop taking them.
Preclinical studies in animal models provided evidence for this potential benefit. When researchers combined CBL-514 with tirzepatide, a medication used for obesity and type 2 diabetes, the animals experienced greater weight loss than those treated with tirzepatide alone. Furthermore, rats that received both medications regained less weight after tirzepatide was discontinued compared to rats treated only with the diabetes drug.
The researchers hypothesize that eliminating fat cells reduces the body’s capacity to store fat again. With fewer fat cells available, fat may accumulate more slowly after weight loss. Professor Garvey noted that this approach could help patients preserve health improvements associated with weight loss, including better blood pressure, blood sugar, and cholesterol levels.
While animal studies support the theory that destroying fat cells aids in weight maintenance, Professor Garvey emphasized that this specific benefit has not yet been confirmed in humans. Additional clinical research is required to determine if the effects observed in rats translate to people.
The drug was generally well tolerated in the trials. Most reported side effects were temporary reactions at the injection site, including pain, swelling, and redness. These reactions were typically mild to moderate, and no serious adverse events were reported. Existing surgical procedures like liposuction primarily remove subcutaneous fat and do not address visceral fat, making CBL-514 a potential non-surgical alternative for targeting both types of abdominal fat.
Source: ScienceDaily
